Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23640 | 71143;71144;71145 | chr2:178575214;178575213;178575212 | chr2:179439941;179439940;179439939 |
| N2AB | 21999 | 66220;66221;66222 | chr2:178575214;178575213;178575212 | chr2:179439941;179439940;179439939 |
| N2A | 21072 | 63439;63440;63441 | chr2:178575214;178575213;178575212 | chr2:179439941;179439940;179439939 |
| N2B | 14575 | 43948;43949;43950 | chr2:178575214;178575213;178575212 | chr2:179439941;179439940;179439939 |
| Novex-1 | 14700 | 44323;44324;44325 | chr2:178575214;178575213;178575212 | chr2:179439941;179439940;179439939 |
| Novex-2 | 14767 | 44524;44525;44526 | chr2:178575214;178575213;178575212 | chr2:179439941;179439940;179439939 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Q/K | rs547376963  |
0.04 | 0.904 | N | 0.557 | 0.337 | 0.231873229951 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.96E-06 | 0 |
| Q/K | rs547376963 |
0.04 | 0.904 | N | 0.557 | 0.337 | 0.231873229951 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| Q/K | rs547376963 |
0.04 | 0.904 | N | 0.557 | 0.337 | 0.231873229951 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| Q/K | rs547376963 |
0.04 | 0.904 | N | 0.557 | 0.337 | 0.231873229951 | gnomAD-4.0.0 | 2.56507E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.79042E-06 | 0 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Q/A | 0.5826 | likely_pathogenic | 0.5834 | pathogenic | -0.143 | Destabilizing | 0.86 | D | 0.595 | neutral | None | None | None | None | N |
| Q/C | 0.9141 | likely_pathogenic | 0.9204 | pathogenic | -0.235 | Destabilizing | 0.998 | D | 0.766 | deleterious | None | None | None | None | N |
| Q/D | 0.6234 | likely_pathogenic | 0.6172 | pathogenic | -0.01 | Destabilizing | 0.974 | D | 0.563 | neutral | None | None | None | None | N |
| Q/E | 0.1523 | likely_benign | 0.1553 | benign | -0.033 | Destabilizing | 0.922 | D | 0.574 | neutral | N | 0.456033194 | None | None | N |
| Q/F | 0.9694 | likely_pathogenic | 0.9723 | pathogenic | -0.523 | Destabilizing | 0.043 | N | 0.481 | neutral | None | None | None | None | N |
| Q/G | 0.3667 | ambiguous | 0.3548 | ambiguous | -0.272 | Destabilizing | 0.926 | D | 0.657 | neutral | None | None | None | None | N |
| Q/H | 0.4837 | ambiguous | 0.5135 | ambiguous | 0.061 | Stabilizing | 0.99 | D | 0.615 | neutral | D | 0.52595464 | None | None | N |
| Q/I | 0.9382 | likely_pathogenic | 0.9439 | pathogenic | 0.106 | Stabilizing | 0.915 | D | 0.747 | deleterious | None | None | None | None | N |
| Q/K | 0.1928 | likely_benign | 0.2023 | benign | 0.01 | Stabilizing | 0.904 | D | 0.557 | neutral | N | 0.418267027 | None | None | N |
| Q/L | 0.481 | ambiguous | 0.4996 | ambiguous | 0.106 | Stabilizing | 0.698 | D | 0.632 | neutral | N | 0.496594525 | None | None | N |
| Q/M | 0.7554 | likely_pathogenic | 0.7629 | pathogenic | -0.111 | Destabilizing | 0.978 | D | 0.615 | neutral | None | None | None | None | N |
| Q/N | 0.4416 | ambiguous | 0.4509 | ambiguous | -0.394 | Destabilizing | 0.993 | D | 0.599 | neutral | None | None | None | None | N |
| Q/P | 0.4882 | ambiguous | 0.492 | ambiguous | 0.047 | Stabilizing | 0.99 | D | 0.706 | prob.neutral | N | 0.496767883 | None | None | N |
| Q/R | 0.1824 | likely_benign | 0.1941 | benign | 0.247 | Stabilizing | 0.966 | D | 0.564 | neutral | N | 0.45424647 | None | None | N |
| Q/S | 0.4331 | ambiguous | 0.4309 | ambiguous | -0.36 | Destabilizing | 0.926 | D | 0.532 | neutral | None | None | None | None | N |
| Q/T | 0.5864 | likely_pathogenic | 0.5992 | pathogenic | -0.25 | Destabilizing | 0.926 | D | 0.62 | neutral | None | None | None | None | N |
| Q/V | 0.8232 | likely_pathogenic | 0.8337 | pathogenic | 0.047 | Stabilizing | 0.86 | D | 0.654 | neutral | None | None | None | None | N |
| Q/W | 0.9221 | likely_pathogenic | 0.927 | pathogenic | -0.609 | Destabilizing | 0.998 | D | 0.745 | deleterious | None | None | None | None | N |
| Q/Y | 0.8713 | likely_pathogenic | 0.8828 | pathogenic | -0.304 | Destabilizing | 0.915 | D | 0.663 | neutral | None | None | None | None | N |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.